Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

Huang, Yunxin; Magdaleno, Susan; Hopkins, Rachel; Slaughter, Clive A.; Curran, Tom; Keshvara, Lakhu

doi:10.1016/j.bbrc.2004.04.023

Cited by 70 publications

(76 citation statements)

References 39 publications

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“…This leads to the recruitment and activation of additional activated non-receptor tyrosine kinases allowing the activation of a cytosolic kinase cascade, beginning with Phosphatidylinositol-3-kinase (PI3K), Akt/PKB and mTor, and ending with the inhibition of Glycogen synthase kinase 3β (GSK3β), one of the main kinases that phosphorylates the microtubule-stabilizing protein Tau Hiesberger et al, 1999;Beffert et al, 2002;Ballif et al, 2003;. While phosphorylated Dab1(Y185,Y198) preferentially activates the PI3-kinase/Akt pathway, phospho-Dab1(Y220,Y232) recruits Crk/CrkL-C3G complexes which in turn stimulate Rap1 (Ballif et al, 2004;Chen et al, 2004;Huang et al, 2004;Feng and Cooper, 2009). …”

Section: The Reelin Signaling Pathway In the Developing And Adult Brainmentioning

confidence: 99%

Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases

Knuesel

2010

Progress in Neurobiology

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Section: The Reelin Signaling Pathway In the Developing And Adult Brainmentioning

confidence: 99%

Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases

Knuesel

2010

Progress in Neurobiology

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“…Tyrosine-phosphorylated Dab1 acts as a hub to recruit different Src homology 2 (SH2) domain-containing proteins, including the p85 regulatory subunit of phosphatidylinositide-3-kinase (PI3K), cellular adaptors CrkL, Crk, Nckβ and SOCS (suppressor of cytokine signaling) [30,[33][34][35][36][37]. Different tyrosine residues appear to interact with distinct SH2 domains: Y 220 and Y 232 are required for the recruitment of SH2 domains from Crk, CrkL and Nckβ adaptor proteins [30,[35][36][37], whereas Y 185 and Y 198 are necessary for the recruitment of PI3K and SOCS SH2 domains [33][34].…”

Section: Dab1 Is a Crucial Cellular Adaptor In Reelin Signalingmentioning

confidence: 99%

“…Different tyrosine residues appear to interact with distinct SH2 domains: Y 220 and Y 232 are required for the recruitment of SH2 domains from Crk, CrkL and Nckβ adaptor proteins [30,[35][36][37], whereas Y 185 and Y 198 are necessary for the recruitment of PI3K and SOCS SH2 domains [33][34]. Tyrosine-phosphorylated Dab1 also interacts with the microtubule associated protein, Lis1, albeit in a SH2 domain-independent manner [38].…”

Section: Dab1 Is a Crucial Cellular Adaptor In Reelin Signalingmentioning

confidence: 99%

“…Dab1-Crk-C3G-Rap1-cadherin pathway Reelin promotes Dab1 (at Y220 and Y232 tyrosine phosphorylation sites)-Crk interaction, induces tyrosine phosphorylation of C3G (a guanine nucleotide exchange factor for Rap1) and activates the small GTPase Rap1 [30,34,[36][37]. Ablation of CrkII −/− CrkL −/− in mouse cortex generates a reeler-like phenotype without affecting Reelin-induced Dab1 tyrosine phosphorylation [39].…”

Section: Dab1 Tyrosine Phosphorylation Activates Downstream Signalingmentioning

confidence: 99%

“…YQXI motifs are important for both turning on and turning off downstream pathways by activating PI3K-Akt and triggering Cul5-mediated proteasome degradation of Dab1 [33][34]. YQVP motifs appear to be critical in recruiting Crk and Nck adaptors to form a signaling scaffold complex [30,[34][35][36][37].…”

Section: Alternative Splicing Regulates Dab1 Function Alternative Splmentioning

confidence: 99%

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Reelin-Disabled-1 signaling in neuronal migration: splicing takes the stage

Gao

Godbout

2012

Cell. Mol. Life Sci.

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Reelin-Disabled-1 (Dab1) signaling has a well-established role in regulating neuronal migration during brain development. Binding of Reelin to its receptors induces Dab1 tyrosine phosphorylation. Tyrosine-phosphorylated Dab1 recruits a wide range of SH2 domain-containing proteins and activates multiple signaling cascades, resulting in cytoskeleton remodeling and precise neuronal positioning. In this review, we summarize recent progress in the Reelin-Dab1 signaling field. We focus on Dab1 alternative splicing as a mechanism for modulating the Reelin signal in developing brain. We suggest that correct positioning of neurons in the developing brain is at least partly controlled by alternatively-spliced Dab1 isoforms that differ in the number and type of tyrosine phosphorylation motifs that they contain. We propose a model whereby different subsets of SH2 domain-containing proteins are activated by different Dab1 isoforms, resulting in coordinated migration of neurons.

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Migration of sympathetic preganglionic neurons in the spinal cord is regulated by reelin‐dependent Dab1 tyrosine phosphorylation and CrkL

Yip

Kronstadt-O'Brien

Capriotti

et al. 2007

J of Comparative Neurology

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The actions of Reelin in neuronal positioning in the developing cortex and cerebellum are relayed by Src-family kinase (SFK)-mediated phosphorylation of Dab1. Biochemical studies show that after phosphorylation Dab1 binds to an adaptor protein, CrkL. Whether CrkL is important for Reelin signaling in vivo is unknown, because crkl(-/-) embryos die before cortical development is complete. In the developing spinal cord, Reelin and components of its signaling pathway, VLDLR, ApoER2, and Dab1, control the positioning of sympathetic preganglionic neurons (SPN); however, it is not known whether SFKs or Dab1 tyrosine phosphorylation is required. In the present study, we asked whether Reelin-controlled SPN migration depends on tyrosine phosphorylation of Dab1 by SFKs and whether CrkL is involved in SPN migration. To answer these questions, we examined the location of SPN in various mutant mouse embryos. Results showed that, in dab1(5F/5F) embryos, which express a nonphosphorylated mutant of Dab1, and in src(-/-)fyn(-/-) double knockout embryos, the location of SPN is identical to that of reeler. These results show that tyrosine phosphorylation of Dab1 by SFKs is required for Reelin-regulated SPN positioning. In addition, we found that SPN migration in crkl(-/-) showed a partial reeler phenotype, suggesting a partial loss of response of SPN to Reelin signaling. These results suggest a role for CrkL in the Reelin signaling pathway to control neuronal migration.

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Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

Cited by 70 publications

References 39 publications

Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases

Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases

Reelin-Disabled-1 signaling in neuronal migration: splicing takes the stage

Migration of sympathetic preganglionic neurons in the spinal cord is regulated by reelin‐dependent Dab1 tyrosine phosphorylation and CrkL

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